ICON Public Limited Company (ICLR) Earnings Call Transcript & Summary

Hi, everyone. Thanks so much for joining us today. I'm Amy Raymond, Senior Director of Therapeutic Expertise at the Center for Rare Diseases, here to spend some time with some of my favorite people as well as all of you, focusing on patient-centric trial development tool kit for rare diseases. Next slide, please. So in addition to thanking all of you for attending, I really want to say a big thank you to CISCRP for all that you do for education, for making clinical research more accessible to the community at large as well as creating this forum for information sharing such as this discussion today, where we'll focus on our patient-centric trial development tool kit for rare diseases. And following a presentation by the both of us, we'll have a lively panel discussion. [Operator Instructions] If we aren't able to get through all of your questions during our time together, we'll be sure to follow up directly after this session. Next slide, please. As I said, I'm Amy Raymond, Senior Director of Therapeutic Expertise within the Center for Rare Diseases at the new ICON, a top-tier contract research organization, a CRO, executing the clinical trials on behalf of sponsors and doing it with excellence. In my role, I collaborate with sponsor teams and clinical operations to drive successful rare disease clinical trials. I'm joined today by Laura.

Thanks, Amy. Good morning, good afternoon. I'm Laura Iliescu, Associate Director of Patient Advocacy Strategy in the Center for Rare Diseases. I lead the patient advocacy strategy team. And what our team do is something quite unique in the CRO space. We work with sponsor companies, so with drug development companies to make sure that they are working with and engaging with patient communities and bringing them into the fold of clinical development. Sometimes, they don't have patient advocacy strategy personnel, and we act on their behalf. And sometimes they do, and the patient advocacy strategy team require extra assistance because there's a lot to do during clinical development, and that's when we come in to support them in implementing their plans. And I also have the pleasure of working with Amy every single day.

Every day. Thank you, Laura. Before we get started, we'd like to learn a little bit more about each of you. So we have a poll we'd like to deploy here. In your company, patient input into clinical trial drug development is, and there are a number of options there, which of those seem most appropriate to your situation and describe a little bit more about the context in which you arrive today? And we'll trust Melissa to know when most people have answered. Great.

And we did see those panel -- that first poll, which had quite a spread across. I think something like 20% said that it was always sought, which is great to see. And then there were quite a few that fell into all of the other categories, which means less than always, which is less than ideal.

All right. Thanks for pairing and sharing on that one. And apparently, I'm back, technology resolved. To provide a little context, this tool kit is one of the dividends of our center's collaborative innovation group. So within the Center for Rare Diseases, we have 2 distinct yet complementary expertise. And I think those are well embodied by Laura and myself, folks like me who are on the therapeutic expertise side of the house. Most of us come with pharma and biotech experience. We're certainly experienced trialists. Our focus is on the strategy and clinical operations. Luckily, we're partnered with patient advocacy professionals such as Laura also coming from pharma and biotech, bringing a wealth of rare disease patient advocacy experience. And we collectively work alongside our Rare Disease Advisory Council. So these are an external group of advisers who are serving in a voluntary capacity together for a 2-year tenure, really guiding what we do, and they're motivated to join us in finding a way to move the needle for rare disease drug development. Next slide, please. So in our time together here, we'd like to cover why we found it necessary to create this tool kit. How we went about that development process, and most importantly, for each of you, what is in the tool kit and how sponsor teams and all of the additional champions of patients' interest can leverage these tools. Next slide, please. So the reality of clinical research today. It's hard, right? It's hard, but it is exactly how we bring new treatments to the people who are waiting. We know that even before COVID, half of our trials were challenged for recruitment. There are loads of drug developers out there who are passionate, who are driven, who are experienced, who understand the urgent need of these treatments, yet a huge chunk of these trials are delayed due to these recruitment challenges. We also see frequently protocol amendments. And there are times when that's unavoidable, and yet some of them, it really was avoidable. So that was a huge time cost and budgetary costs. We know that very few rare disease patients live near the clinical research sites that are typically used, which creates an inherent burden traveling to and from the clinical research site. We know this is true sort of intuitively, right? But we also have structured data that comes from our own surveys of the rare disease patient community, hundreds of rare disease patients across different therapeutic areas, all saying this is the #1 challenge they face in trial participation. It's not the only one, though, because here's a great quote from a family who has taken part in more than one clinical trial and really provides encouragement and support to other families going through the same that even when a patient wants a new treatment -- and it's still stressful, it's scary, it's time consuming to take part in a trial. And that is from somebody who -- this isn't her family's first trial. So we know that it's true across the board, "We know that we don't have time to waste because there are hundreds of millions of people waiting around the world, that half of our rare disease patients are children, many of them with life-limiting disease that we really need to develop more meaningful treatments for, and that over 90% of our rare disease [indiscernible] do not have a single FDA-approved treatment available today." And I imagine a great many of us focus our careers on solving that very, very dilemma. Next slide, please. And as much as that was a little doom and gloom, not very encouraging, the truth is there's a lot of things that the existing practices do really well, and thank goodness, right? Those are things like regulatory-compliant protocols, things like ensuring high scientific integrity that we're collecting interpretable data, all of these things that go into understanding what was the value of that drug intervention. But we do recognize that there are lots of things that are not being done by these standard practices. It's not collecting that participation burden knowledge. It's not necessarily making sure that the trial is feasible from the participant family's perspective and a lived reality of having that disease as well as the lived reality of taking part in that study. We need to do a better job of optimizing the participant experience and recognizing the participants' key role in the effectiveness of the trial. Next slide, please. So the traditional paradigm, starting on the top left, there's a protocol, sites are selected, there's an approval process. We trust those sites to have all of the responsibility of recruiting those participants. There's data, thank goodness. That is the output, which gets presented and published, ultimately landing with the regulators, data filed in registration. But what's missing here is it lacks patient involvement. It leaves a lot of gaps in understanding about what is truly feasible, practicable, acceptable and, frankly, desirable for intended participant families. Why is that? Next slide, please. Well, we know that regulators are very supportive of patient involvement and trial design and conduct. These are some screen captures of documents I bet many of us have seen before, coming from the FDA, coming from the EMA, really highlighting the value of patient input into drug development. It's not a concept unknown to our regulators. They're suggesting it, not yet requiring it, but they're certainly supportive. Next slide, please. We also know from experience, including peer-reviewed published literature presenting a strong business case for patients' involvement. It's not a trivial thing if you can really speed the time lines, if you can make a trial more efficient. It has dividends for every single stakeholder in the entire process. Shown here are just a smattering of publications that are available on this very topic, all coming to the same conclusion. On the next slide, we know that trial patients don't have a seat at the table. But why is that? And why are more companies not doing more often? Well, we recognize that there is a disconnect, right? But patient engagement is broadly recognized as a critical success factor. An increasing number of sponsor teams include patient advocacy professionals. But this is a newer way of working for many folks, and we're all sensitive to the compliance concerns, but being averse to perceived risk coming from any patient contact, those are actually driving real risk to recruitment, to retention, to making study participation achievable for participants and their whole families. Change is hard, but the dividends are real and significant. Next slide, please.

So the question we asked ourselves is, all of us coming -- in the Center for Rare Disease, many of us come from industry, and we have been on the industry shoes and worn different hats in the industry, we said, "Well, what is then stopping -- what is -- what are some of the things that are stopping companies from overcoming some of these barriers that Amy had on her last slide and coming to a place where all the companies that we work with for the hundreds of rare disease clinical trials that we do are engaging with patients effectively throughout their clinical program development life cycle?" And so we took a step back to look at that because we don't believe it's lack of will and we don't believe it's for lack of regulatory support or for lack of a business case. But we do understand that there is a process and a system change -- systemic change that is required in order to do it. So we took a step back and looked at it from a different perspective to see if we could come up with something insightful and asked ourselves fundamentally, "What is a clinical trial?" And at its most fundamental, a clinical trial is an interactive system. And really, that just means that it's a combination of humans and technologies and processes that almost work together efficiently, and every component of that system has to work together efficiently for a clinical trial to begin and recruit and enroll and proceed with adherence and meet its milestones and end on time and bring a meaningful treatment to patients who are waiting. So fundamentally, it's an interactive system. Next slide, please. So continuing to look at it from a traditional clinical development model, so sort of that traditional paradigm versus looking at it through, say, a systems engineering or a human factors engineering paradigm -- I happen to have a human factors engineering background, you start to see a discrepancy between these 2. So in the traditional paradigm of clinical research development, there's an underlying assumption that the active stakeholders whose activities have an impact on the efficiency of the trial are really the medical professionals and the sites. So sites and HCPs are believed to be active stakeholders in the traditional model, whereas patients and caregivers, who are participating in this study, really considered to be passive subjects without really any ability to -- or any real means of influencing the efficiency of that system or that study, whether it was going to work out well. And so what we have is a situation where our clinical development ecosystem has evolved in such a way that sites and medical professionals, their constraints and their ability to function within that system and whether that system enables them, we have really strong processes for assessing that upfront, and we have great predictive tools. We have feasibility that can be done, and that's a very familiar, well-worn process for any CRO to perform. But we don't have the same thing for the actual participants. So although patient engagement and involving patients is something that patient advocacy professional like ourselves are doing to different degrees and different companies, there weren't really anything -- there wasn't really anything as systematic that people could look to or that companies could look to, to say, "Here's a tool that I can use to sort of help me with that process or a set of tools that I can look to, to help surface some of the systematic factors that would be relevant across many rare disease conditions and studies and that I should probably take a look at and assess whilst I'm developing this clinical study, this protocol, which is really just a blueprint for an interactive system that the participant will actually have to have a hand in ensuring that it works efficiently." And that's particularly a problem in rare disease because the constraints of individuals who are affected by rare disease can be extremely difficult to predict if you are not living that life, if you are not living that experience day-to-day. And you can -- whereas in a common condition, you might be able to look to the literature or really trust that your key opinion leaders have the full gamut of insight into what that lived experience is like, that's not something that you can always count on in rare disease. Many, many gaps in literature. And many, many times, the only way to really get those answers is to go directly to the patient communities and to ask them directly about their lived experience and constraints. Next slide, please. So essentially, what we looked at and we thought, well, here is definitely a gap. We did a massive literature search. We scoured left, right and center. We talked to our Rare Disease Advisory Committee and confirmed that there wasn't really anything systematic of that nature that folks could look to -- that could help them to rapidly identify some of these factors that might be universal drivers of burden across different rare disease conditions and that could provide a risk management framework that could perhaps support the process of bringing in patient insight and caregiver input to make that accessible and take some of the friction out of that potentially for teams who might be unfamiliar with processes and best practices and specifically to factor in the very unique things about clinical research that makes it particularly challenging as well as something that they could look to throughout any stage of the trial development. Because individuals confront challenges from protocol design all the way through to study implementation and conduct. And so being the motivated individuals that we are, I extend it for rare disease colleagues and I, along with the Rare Disease Advisory Committee, decided to set out to try to see if we can build them. Next slide, please. I'll just tell you a little bit about our process that we followed. So remember that one thing that's very unique and powerful about our team is that we have Amy's side, who are really focused on the clinical strategy, understand operations to run through, as well as ourselves, who understand collaboration with patient advocacy organizations within the life sciences as well as our Rare Disease Advisory Committee, who are truly experts in their own communities and their own communities' experiences with participation in clinical research but also their -- through their own experiences as well. It's a very powerful group to come together to try to build some of these resources that we hoped to. Next slide, please. So the process for developing the tools that we're going to take you through took about 18 months and involved a series of collaborative workshops, quite a few workshops, quite a few iterations. And I'm not going to bog you down too much with the details of how we approached it. It was very much from a systems engineering sort of development process, which began with scoping, and really coming from the experience of trial participation first, so their contributions and understanding what that model looks like for individuals affected by rare disease, and then layering in expertise around the development of protocols and then the operationalization of those protocols and what that looks like on site. Next slide, please. And I want to say that this was possibly -- one of the things that I'm most proud of in my career to have ever done, not just because the process and the individuals were incredible and their commitment to addressing the challenges of clinical research and elevating clinical research in rare diseases is just incomparable, but because of the insights that came out of it, which were incredibly valuable and, I think, really helped to shape a very powerful set of tools. Among them, I think one of the key insights that came through is when thinking about participation in the clinical trial, this came through from our Rare Disease Advisory Committee, is the paramount importance of daily routine for individuals who are affected by rare disease. In the sense that throughout their day, they are doing things, they need to do certain things in order to get through their day. I should say we, because I, myself -- my family is affected by rare disease. Which means they are using a lot of strategies to cope with the limitations and challenges that exist. There's a lot of things to do to make sure that you can take the medication on time, to get yourself to work, to look after your child, to just get through that day and do the things you need to do through that day. And when you ask someone to depart from that routine -- and that's what a clinical protocol is, you're giving someone a to-do list and you're saying, "I need you to do these things." That's in addition to what they have to do to get through the day, right? "So now I'm going to add to your plate of things that you need to do through the day. And if I add things that make it harder for you to do those things that you do, like, for example, if you're used to -- if your condition has fatigue as a prominent feature and you're used to having rests, lengthy rest period throughout the day, and I ask you to come to a site visit and perform a series of physical test without a period of rest in between, that makes things really hard for you and introduces burden." So that was a really incisive insight that sort of permeates the tool kit and the tools that we're going to present to you. And the other really important insight that I want to point out is that they made it very clear that while these tools that we're developing can be a really powerful start, can really help to shape that engagement and take some of the friction out so that you're focusing it on the aspects of the clinical trial that you need to make sure are acceptable and feasible for patients, they can never replace actually getting information from the rare disease patient community that you're working with. And that's because every community is unique. And while 80% of the challenges are similar, there is always going to be that unique context. So in no way do these tools replace, they really just help to supplement and take some of the friction out of that engagement that does need to take place. Next slide, please. So at the end of our 18 months, we developed 3 tools that we're incredibly pleased to share with you and with the world really on an open source, completely free, no copyright basis because we don't just want our clinical trials to be more accessible for and less burdensome for rare disease patients and get medicines to them faster. We want everybody's trials to do that in rare disease. So the tool kit really consists of 4 items. That first one, the patient involvement value dossier is one for our friends who champion patient involvement in companies where perhaps that's not yet the norm or that's not done consistently and always. And that really is kind of a hard sell. It's a roundup of some of the literature that Amy pointed to that supports that it can definitely make a difference to your bottom line, to decreasing risks, to eliminating costly protocol amendments, to making sure that you hit your milestones on time, to getting you to market faster if the product is successful and effective and perhaps having 2 or 3 extra quarters of revenue. And that's really intended to be a tool to serve your needs to convince and influence inside your organization or if you happen to be a patient organization, you can take that then to advocate to make a case for closer involvement with those companies that are working in your space. The second tool is really, I think, one of the most powerful tools in the tool kit, and that is the patient-centric protocol risk assessment tool that Amy will tell you a little bit more about shortly. But this tool is a very powerful look at and -- that can be applied to any protocol, any rare disease protocol that will take you through and help to identify where you might have drivers of risk that are quite common, including dropouts, including screen failure, high screen failure rates, including protocol amendments. And Amy will tell you about that in a bit. And then 2 companion tools. The first is a rapid participation burden survey, which is a do-it-yourself survey that sponsors are really -- what patient organizations could use as well to rapidly create a survey, which can focus feedback from patient communities on aspects of the clinical program that tend to be drivers of burden and drivers of inefficiency if they're not considered and if patient input isn't brought in to find out whether it's desirable, acceptable, feasible. And finally, the fourth tool, which we'll tell you a bit more about later, is really a tool for prospective participants. And it's really a guide to help them and empower them to ask really tough questions actually when someone presents them with the opportunity to join a clinical trial and to advocate for themselves and the type of participation support needs and making sure that they're asking the questions that are important to them for their daily lives, really going beyond just the old-school, "Have you found out about all of your treatment options?" because there's just a lot more than that to consider in thinking about whether you can fit a trial into your daily life when you are affected by rare disease. Next slide, please. So I will turn it over to Amy to take you through the protocol risk assessment tool.

Terrific. Thanks so much, Laura. Right. So to spend a couple of minutes drilling down into the patient-centric protocol risk assessment tool. It's a little bit of a mouthful, isn't it? Because it was developed jointly by clinical strategists with clinical operations background, folks like myself; as well as patient advocacy experts, Laura; as well as our Rare Disease Advisory Council, those experts, it was literally designed to enable collaboration between patient advocacy professionals and the clinical operations and medical teams in any sponsor house really. So what it does is allows one to surface the potential efficiency risks coming from participation burden. So these are the risks that were historically invisible, right? As many folks really regarded recruitment and retention as a site-level concern, would in fact so much of that impact really derives from the lived experience of a rare disease patient trying to take part in a clinical trial. So using this tool helps to identify those otherwise invisible gaps in knowledge and helps to direct the patient input being gathered to the areas with the biggest impact for each individual protocol. As Laura said, we found that there was a lot of overlap across the diaspora of rare diseases. But we know that they aren't the same challenges from therapeutic area to therapeutic area, not always the same barriers from protocol to protocol. And this allows one to make a protocol-specific assessment of where those gaps are and how to address them. Next slide, please. So this risk assessment tool, it's very structured. It's a Microsoft Excel-based tool that allows protocol developers as well as protocol reviewers with a structured approach to identify the key risks that drive participation -- key risks driving participation burden in any draft protocol at any stage. And it does this by probing 7 different dimensions over 6 distinct risk categories. And in the process of our internal and external expert validation, we found that on average, it took about 15 to 45 minutes, so roughly half an hour to cover the 70 items that touch on all of the key points of the analysis that, again, bubbled up through collaboration with rare disease advocacy leaders. Next slide, please. For a very high-level overview of what the risk assessment items are. So those 70 items really span the 7 dimensions of the patient population. What is the participation value proposition for each individual protocol as well as the protocol elements such as the screening, the scheduled assessment, the study [ does ] experience. Sometimes it's applicable that there's an IP administration element. And more and more, we're seeing wearables and apps are a newer area of drug development that we're all learning in. Not everything goes through user acceptance testing when it's part of a new patient population in clinical trials. Next slide, please. So when and how would one use this tool? Well, it's never too early. And while earlier is, in fact, better, it's also never too late. So starting from protocol development, by starting it early, it allows the team to identify gaps in knowledge about the patient population that can specifically affect study and product success overall. Again, by starting early, we're able to identify protocol and study elements that may not be feasible or acceptable or desirable to that patient community. And knowing it early is incredibly helpful. You are also able to identify where are the areas in that particular protocol where participation support requirements could help support access and minimize recruitment barriers as well as dropouts. But say, for example, you have a protocol that's finalized, a finalized protocol. It's still useful for doing those second two things, identifying the protocol-specific elements that are objectionable to a patient community or even just impractical, right? As Laura pointed out, changes in the daily routine can have a big impact and a lot of participation burden. It still allows you to identify participation support requirements. But even if your protocol's already finalized, it's not too late once you're in the study conduct phase. You can still use this tool during study conduct to identify reasons for what you may be finding as a lack of study efficiency. It's not uncommon that recruitment is challenging in these rare disease drug development programs. So when one encounters that, if they have not already used a tool like this very one, even during conduct of the study, it's useful for identifying really what are the barriers and identifying what are potentially really great operational solutions without necessarily having to change the protocol. Next slide, please. As Laura mentioned, there are a few additional tools in the tool kit. She did a great job, of course, of talking through that patient development value dossier shown on the left, in addition, the DIY survey -- build a survey tool, can be used by sponsors or patient advocacy organizations themselves. Last but not least, on the right there is the what to ask when you're interested in a clinical trial, and it's really meant for the rare disease patient who is considering a specific trial. And I point that out because it's great for a patient education tool, but we also have drug development partners who, with our blessing, of course, it's all open source, have taken this and adapted it to their specific trial and really created a framework for having that discussion at the site level for that particular trial. So each of these tools have a place and a role to play. Next slide, please. As Laura mentioned, this is free, open source and available to all. Shown there on the bottom is that URL where all of our participants and everyone can access these tools. Before we go much further, I would love to stop and take a moment and ask a little bit more of the audience today about your processes in a second poll. So please let us know if you feel your company has any of these varying options. Thank you. I'm assuming I didn't freeze again this time. We'll certainly trust Melissa to know when most respondents have had an opportunity to provide their feedback. Interestingly, we have folks from every point in that spectrum. And hopefully, that means what we've provided here and the discussion we're about to have with our external experts will be helpful. With that, next slide, please. I'll pass it back to Laura.

Thank you very much, Amy. So for the final part of our talk today, we'd love to now welcome our 2 panel guests. Joining Amy and I are 2 exceptional patient advocacy professionals in the life sciences. Just one second. So first, I'd like to welcome Kelli Wright. Kelli has been a passionate patient advocacy professional for more than 15 years and has worked in both the industry and the patient advocacy sector. Most recently, she was Senior Manager of Patient Advocacy at Harmony Biosciences and National Director of Strategic Initiatives at CureSearch for Children’s Cancers. Throughout her career, Kelli has worked with numerous patient communities, patient advocacy organizations and drug development companies. I would also like to welcome Kendall Davis. Kendall has been a very highly regarded rare disease patient advocacy professional for over 15 years and is a familiar face for many in the rare disease advocacy community. She is the Patient Advocacy Lead for Early Development at Spark Therapeutics. Prior to which, she was the Patient Advocacy Strategy Leader at PRA Health Sciences and Director of Strategic Alliances at Global Genes. Kendall also serves on the Board of Directors for Team Telomere and is a strategic adviser to the Rare and Undiagnosed Network. Ladies, welcome.

Hello.

So welcome, Kelli, thank you so much for joining us today. And Kendall, welcome, thank you so much for joining us today. It's wonderful to see you both.

Thanks for having us.

Thank you.

Terrific. So for our panel discussion, we thought we would do something a little bit different, if you're up for it. So we thought we'd first ask you a little bit about using the tool. These are tools that you're both very familiar with and have worked with. And then I thought it might be fun, if you're up for it, to do something a little bit different, which is to have an objection handling round, and Amy, you're welcome to join in on this, where I will throw out some objections to using the tool kit, and you can let me know how you would respond to those.

That sounds great.

Yes. Let's do it.

Terrific. So to start off, I think my first question would have to be, since you are both passionate champions of involving patients, from your perspective, how can this tool kit offer patient advocacy professionals or champions like yourselves ways to advocate for that within their companies for more patient-centric approaches to drug development?

I'm happy to start. So thank you for having me. I started my career for a long time in nonprofit, so being that patient voice from a nonprofit perspective, and then coming into industry, which was a great learn, and I really appreciate all those years as a patient advocate. And so this tool for me now is a way to get the voice of the patients in a very tangible, concrete Excel document to share internally. I think the patient advocacy role in pharma can a lot of times be sharing stories about patients' experiences, which people are very receptive to. But having an actual tool and a document with very specific questions and answers that you beautifully put together is a really great way to make sure that the voice of the patient is being thought about at whatever point in the protocol development and trial development the company is in.

Yes. And I'd have to add, even just thinking about the tools collectively, I think a lot of times, especially if you're working in patient advocacy and a lot of members of the cross-functional teams you're working with maybe don't come or have a background in rare disease, that -- the value is a little bit harder to kind of hone in on and really articulate to members of potential development teams that have been working in much larger indications. So even having something like the value dossier that can point very specifically to instances where utilizing not even just the patient voice, but really their perspective through everything from protocol, concept planning through actual clinical development and actually having tangible, again, examples and metrics to show why this is valuable can be a really great place to start. Because I think a lot of times, we're working with individuals who think very logistically. And they're thinking with regard to, "Okay, what kind of data do we need? How do we get it?" And sometimes, some of the more kind of nuanced or life situations that patients might be facing when they're trying to access clinical research aren't in front of mind. And there's nothing wrong with that, but I think this tool provides us a really great opportunity to bring that into the fold and actually have it be a part of the creation of clinical development programs from a much earlier time point.

And that's a great point, Kendall, because being in the patient advocacy role, we have the privilege of talking to patients all day and every day and understanding what it's like to live with that disease. And our colleagues don't, not because they don't care, but because that's not what their job is, right? Like that's our job to do that. And so for us to be able to look at this document and say, well, I know I -- based on my conversation with the patient, I know that this could be an issue. This document just reinforces that because we're able to have that come from the patient and have our other colleagues think about the patient perspective that we have the honor of hearing every day to bring it into their part of the business.

And I mean, Amy and Laura, like jump in here, but I think it also provides the opportunity for us to contextualize the patient experience in a way that is a little bit more accessible to some of our cross-functional teams. And I think that's really -- when you're talking about trying to engage early and actually bring in the perspective of patients or communities or caregivers at a much earlier time point, that can be difficult because, again, we're all looking at information in our specific way. And so I think this tool kind of bridges some of those decides and allows for that conversation to happen a little bit more effectively.

I completely agree, Kendall. It sort of makes the data objective rather than subjective. It allows it to be about the data rather than the source of the data. I think that it gives it a little more currency.

Great. Thank you, ladies. My next question to you both is a little bit around the practicalities of using the tool kit internally. And I would love it if each of you would share a little bit about your experiences and ways that you think are really good ways to use and champion the tool kit internally within a development team to bridge some of those gaps and any best practices that you would share with others who might be thinking about bringing the tool kit into their own companies.

Kelli, I'm going to let you start because you've actually executed this, and then I can kind of give my two cents about -- from my perspective and what I've actually done so far.

Happy to, yes. When Laura shared this, I was really ecstatic to see this tool for all of the reasons we just talked about. And so I have used it in the past by internally championing, getting some Management Board, which I think is a really important thing to star and asterisk, is to, as much as you can, get as high as you can to have buy-in on this. So we had buy-in from VP and CMO level to utilize this tool. And so this was used pre Phase I, so really getting in as early, almost as early as we could, and completed by our medical and clinical team. And from that, we were able to host an internal Patient Advisory Board in which I had reviewed the answers to all of the questions, saw where there were open questions from our team, where there might be some opportunity for patients to help kind of give a little more information as to what it is, why that may or may not work for them and then use that in the discussion guide for the Advisory Council. So the team completed it. I saw my colleagues in medical and clinical completed it. I -- so my colleagues in medical and clinical completed it. I used it in patient advocacy. We executed it through patients and caregivers through an internal Advisory Board. And then from that, I look at it as really a long-standing tool in that it was a great first step to get the information in. From there, we were able to put feedback that came from the Advisory Board against the areas that we still had questions on. And then the hope would be to continue it to track it along the way and see if there -- I think in patient advocacy, kind of to your point, Amy, it's hard with data sometimes to -- it's very much storytelling and sharing experiences and not as data driven. And so this allows us to really track along the way to say we identified that this might be an issue. We fixed it in the way we developed the protocol or how we worked with sites. And therefore, we've had high retention because of it or whatever it might be, but being able to track that throughout the whole development process from a patient advocacy perspective, I think, just brings more value to our function within organizations to be able to show the value, where we know where there's value in patient, bringing a patient perspective, this is a concrete way of showing that.

Yes. I am obsessed with that example. I think it is so cool that you'd kind of move through the entire process. And I can't for the life of me remember who said this. But someone said what storytelling is just data with a soul. And so I think we really as advocacy professionals have to figure out ways to make that a reality. And so something that I'm doing working in early development is really kind of working to understand the ways that my cross-functional team members and colleagues think about the potential benefit of working with patients because I think the more that we can understand where our medical, clinical dev teams, where they're coming from, the more we can try to provide them with resources and with examples of how working with advocacy could meet some of these questions or issues that we're having. And I think that Kelli just explained a really beautiful way that we did this so that she did this within her company, where she started really early. And that buy-in isn't always easy. I think that sometimes can be one of the biggest hells, but I would say it's a hell to die on if you're working in advocacy because that type of internal champion can be just incredibly helpful throughout the process. And I think the more that we can provide tools and resources like this, the easier that fight becomes.

So my next question is really around tailoring because the tool kit can be tailored. It was built to -- so that companies can take it and to some extent, tailor it to their own needs. I wonder if you, either or both, would be able to share a little bit about any tailoring that you might be looking to do or did to shape those tools around your own needs to fit them best.

I triple-checked with Laura that I could edit it before I did. But from -- I think all of the tools are really wonderful. The one that I honed in on was the risk assessment document. So I took that and really pulled out that one tab that we saw on the slides before with the yes, no and all of the groups. I turned it into the company's colors. There is an option to put the NTT number on and just really personalize it as much as you want for the program and went through -- and I didn't edit any pieces. The next time I would use it, I might go back where -- I knew that our trial didn't have a ton of wearables. And so removing that might be something that -- to really make it as condense as possible for the medical and clinical teams to remove that. But it's amazing to have the ability to do that. So thank you both for that. But just really making it feel a bit more to our company -- the company. And then I also added a note section so that when the team was completing -- when you complete it, if you say yes, no or not applicable, it will prompt you with some feedback, which is really helpful. On top of that, I added notes, which allowed the team to put in any questions or clarify or -- and I got some that were like, "I hadn't thought about this. We need to think about this more," which was great. So that note section. And then that, to my point before, of adding on would be feedback from Advisory Board as a column and then entering that information and then doing a check in or whatever the next steps are for your protocol. That's how I edited it. It wasn't a ton of things. It was kind of minor, but it was wonderful to have the ability to do that and just make it feel more internal for the company with our branding and colors and personalization to what we knew so far were the protocol was.

I mean I don't even know that I can add much to that. I think being -- having a tool that you can make a company feel really comfortable with based on whatever there -- even internally, the types of potential compliance factors that may be in play or if you're going to be using it with an external Advisory Board, just being able to do that and to make it your own and customize it so that you're comfortable with the information being asked, presented, all of that, I think, is just -- I mean, it's just a really valuable asset that this tool has that I think will make it a lot easier for companies to get more comfortable adopting.

I do think -- this is not exactly answering your question. But I do think it's important, it came to mind, that when you share the tool kit, to make sure folks know that it is from a patient perspective because we know that our colleagues do a lot of risk assessment documents to make sure that the trial is as sound as possible. And this is not competing with that. It is not to conflict with that. It is truly to enforce that this -- have we thought about it from the patient's daily life? Does this patient population need a caregiver? Or do they need to have breaks throughout the day? Those type of things, that's what's in this risk assessment document. So maybe having a meeting about it, not to add another meeting, but to walk through your team to really show that you're not challenging them on any point. It is truly to just bring the patient perspective as they're developing the trial.

Thank you so much, ladies. So we've got a few minutes left. And if you are still up for it, I would love to do a lightning ground of objection handling, some of the things that I'm sure you've heard along the way. And Amy, I would love for you to join into the fun. So something that you may have heard, and put your hand up if you've heard this one before, "We're too far along in our program, and we already have a protocol." Amy, as our clinical lead, go for it.

Oh, sure. So how would I recommend somebody handle that objection? Well, if we're too far along to handle changes at this point, that may be entirely true. If your recruitment is going better than you anticipated, if your retention is doing phenomenally, may not be any need for change. If however, your time line experience or even feedback from the clinic suggests actually something does need to change, the changes don't necessarily have to be to the protocol, right? Using a tool like this, even in conversation with the patient community, helps one understand why is this not their trial of choice. Even if it's their trial of choice, why are they not able to participate? So often, you can work with your CRO to introduce operational solutions even if a protocol amendment is not called for.

And then in turn, might that help with retention, too. Can you identify those pieces of why patients might not be able to stay on the trial?

Exactly. Great point, Kelli. Great point.

All about the mitigation, right? I mean if we know we can't make changes, if we can still identify challenges, then we can at least be thinking about ways to address those challenges if, in fact, we get to them because it's most likely going to happen. And it does. I mean I feel like that's kind of clinical research in a nutshell. But tools like this, I think, really do help you to be able to think through potential barriers within a protocol or challenges so that we can kind of be ready to go with some solutions that we don't lose individuals that are participating and we don't lose potential participants because we haven't figured out a way to address potential questions they have about challenges that they see.

Well, that's definitely convinced me. Our next objection, which we hear quite almost as frequently, "We're too early in our program. It's too soon."

You can never be too early ever, right? An ideal situation, which compliance and legal would love, is to introduce patient advocacy when you're thinking about buying a new drug or buying a new [indiscernible], right? Is it needed in the patient population? So there really can never be too early of an opportunity to bring a patient perspective into your company.

Completely agree. And I mean there's always going to be pushback, but I think that, "We're too early" leads to questions around, "Okay, well, we can't provide insight into our protocol design yet or we have to keep things kind of under wraps." But I think there are definitely ways to still get the insights that you need without...

Divulging the protocol.

Yes. Without like, exactly, complicating or threatening the integrity of the program.

100%. And I experienced some of that actually because there was a lot of back and forth -- all the advisers were under confidentiality because the program wasn't public yet. And so it was a very selected group that were under CDA from before that we had already had relationships with. So there was a level of trust there. And it was, do we show the protocol? Can we show the protocol? What does that mean? Like how do we get there? And so where we landed was to not show the protocol. However, as a company, we knew what the questions were. How would someone feel about this type of trial if they had to withdraw from some -- they had a withdraw period, how would -- what would that feedback be? And so the questions that we asked were broad about clinical trials and about different types and ways that clinical trials are done that weren't specific to the program that we were working on, that weren't specific to our protocol, where we didn't actually share the protocol, but we still got the answers that we needed to then take back into the design of the company's protocol. So there's absolutely a way to do it.

If I could just -- the story you just told is so beautiful. I want to point out that the story you just told was engaging with the community, even if it wasn't on the granular level of protocol, having that iterative feedback actually strengthened the relationship with the patient community. I'm just sort of being [indiscernible] you said.

Oh, yes.

And if it's early, it's never too early to build those relationships.

I mean the patients were thanking me for including them, when my thanks was to them for taking the time out of their day, which was a significant ask of, of this rare disease population. And so it's also about, I think -- and we do this often, is continuation of that relationship building, is, "Thank you for giving your time." And of course, they were paid for it. But then following that, summarizing the key insights and reaching back out to them to say, "We want to make sure that we heard you correctly." Like, "Is this accurate in what you -- how you feel about your disease and how it's represented and what would be -- would make for a good trial." And then letting them know the day before we make the trial announcement so that they have an insight. So all of those small pieces allow for long-standing relationships as you're getting into a new disease community or whatever the reason is, but absolutely, Amy, I mean, everyone was so thankful to be able to be included. And I honestly don't think the confidentiality is a concern because everyone is so excited to be included, they're not going to tell anyone. They want to keep -- they want you to keep coming back to ask for them to participate with you. So from a patient adequacy standpoint, I think it's great.

And the burden survey tool, the participation burden survey tool does just that. It helps you to write questions that don't divulge your protocol, but are asking about what would be involved from the patient, what they would have to do in order to fulfill your protocol requirements. So it's a really neat way of not laying out your protocol in front of folks and giving your clinical teams and compliance teams some comfort. You've actually been so effective that you've already handled my objection about confidentiality. My last objection, which I'll throw out there is, "We already developed the protocol with KOLs. Lots of KOL input here."

Are the KOLs going to be your trial participants? If so, you are going down the right road. I mean this is -- I think that obviously, KOLs, the clinicians and physicians in these spaces, are -- they're invaluable and you absolutely have to utilize them in protocol development. But they're still not going to be able to tell you how an individual is going to be able to access the trial. They might be able to give you their idea or their prediction. But at the end of the day, like there's just no way to get at how a patient is going to engage with your clinical trial unless you ask them.

And Kendall, you have a wonderful phrase for patient advocates to be brought to the same level as a -- please share.

Patient advocate opinion leaders. I always ask them like, "Well, did we talk to the patient advocate leaders?" Like, "We've talked to the KOLs. What about the other very large cohort that exists in that space?"

Because if you're talking to -- at any -- whatever point you're talking to a KOL, you should also be talking to a key patient opinion leader at the same time.

What a beautiful closing thought. Thank you so much, Kelli, Kendall, Laura, all of you for the time today as well as the opportunity to share with you a little bit about this tool kit. If you have any questions, you are most welcome to follow up with myself, with Laura Iliescu. If you're interested in learning more about the tool kit, maybe having a training session for your team, let us know, we're happy to do it. Well, thank you again, everyone, for all of your time today. Have a wonderful rest of your day.